NIAID Pedigreed Rabbits Seeking New Homes

A largely closed colony of rabbits developed, bred, and characterized at the National Institute of Allergy and Infectious Diseases (NIAID), NIH, is available particularly to sites where breeding colonies can be established.

A relational database developed with the computer program 4D contains more than 45 years of breeding records and other information about animals in the colony. The NIAID allotype-defined rabbits have polymorphisms of a variety of genes involved in immunity, including genetic variants (allelic allotypes) of the VH, CH, and CL regions of antibody molecules. The colony also contains descendants of rabbits formerly at the Basel Institute for Immunology that include the VH1a2-deleted Alicia mutants (ali), the CK1 splicing defective Basilea mutants (bas) and several VH-CH recombinant heavy chain types. Also contained are VH-CH recombinants discovered at NIAID (2R1 and 1R2) and the parental (2R1 and b9k) wild-type of the two mutations observed in Basel (ali and bas). The mutant ali animals have a known deletion of a key variable region gene in the immunoglobulin heavy chain locus that is present in the related wild-type 2R1. These animals may differ in susceptibility to infectious diseases because the mutant ali has abnormal delayed development of humoral immunity.

Among the many strains in the colony, those with the b9 kappa light chain allotype have been very useful for many people making high affinity rabbit antibodies directed toward defined epitopes that can be selected by phage display for particular specificities. Rabbits have been used as the starting source of potential humanized therapeutic monoclonal antibodies and of diagnostic reagents because they produce highly specific antibodies with high affinities. When rabbits of b9 type were immunized and recombinant rabbit-human Fab generated by phage display, yields of distinct and specific high affinity Fab increased -- see Popkov, M., et al J. Mol. Biol. 325: 325-335, 2003. An improved vector and other references can be found in Hofer, T., et al. J. Immunol. Methods 318: 75-87, 2007.

The January 2006 document "Increasing sequence coverage from 2x to high coverage (6-7x) for selected mammalian species," which recommends that rabbit be sequenced more deeply than the current 2x coverage, includes a description of the NIAID Rabbit Resource at p.14. See http://www.genome.gov/Pages/Research/Sequencing/SeqProposals/2x-7x_promotion_seq.pdf.

Also of interest are two websites about rabbit resources, one maintained by the National Center for Biotechnology Information (NCBI), http://www.ncbi.nlm.nih.gov/projects/genome/guide/rabbit/, and one by NIAID on Rabbit in Immunology & Infectious Disease, http://www3.niaid.nih.gov/research/resources/ri/.

The latter site offers a summary of an NIAID workshop on Rabbit Models of Human Infectious diseases held in 2005. A second workshop of broader scope is in the planning stage.

For a recent Rabbit Immunoglobulin Genetics review, see: Mage, R. G. et al: B cell and antibody repertoire development in rabbits: the requirement of gut-associated lymphoid tissues. Develop. Comp. Immunol. 30: 137-153, 2006.

For a paper describing a group of rabbits being selected and bred for responses to immunization leading to a model of human Systemic Lupus Erythematosus, see: Rai, G. et al: Models of systemic lupus erythematosus: Development of autoimmunity following peptide immunizations of noninbred pedigreed rabbits. J. Immunol.176: 660-667, 2006.

For more specific information and to arrange to receive some of these animals please immediately contact:

Rose G. Mage, Ph.D.
Chief, Molecular Immunogenetics Section
Laboratory of Immunology, NIAID
Bldg 10 Rm 11 N 311
10 Center Drive MSC 1892
National Institutes of Health, Bethesda MD 20892-1892
E-mail rmage@niaid.nih.gov
Tel 301 496 6113
FAX 301 496 0222